Bag-1 Expression in Hyperplastic and Neoplastic Prostate Tissue: Is There Any Relationship with BCL-Related Proteins and Androgen Receptor Status?

Abstract

Aims and Background

To evaluate the function and distribution of BAG-1 protein in hyperplastic and neoplastic prostate tissue and establish the relationship between this protein and BCL-related proteins (BCL-2 and BAX), androgen receptor (AR) expression and chromogranin A.

Methods

Twenty-eight prostatic adenocarcinomas and 16 prostate hyperplasias were included in this retrospective study. BAG-1, BCL-2, BAX, androgen receptor and chromogranin A immunostaining was performed by means of standard avidin-biotin peroxidase methods. The M30 antibody was used to identify preapoptotic and apoptotic cells. The immunohistochemical histological score (HSCORE) semi-quantative system was used to evaluate immunohistochemical staining.

Results

Statistical analysis showed a significant difference in HSCOREs of BAX, M30 and AR between the carcinoma and hyperplasia groups. Carcinomas expressed higher HSCOREs of these markers than hyperplasias. There were significant differences in nuclear and cytoplasmic BAG-1 positivity between high and low-grade carcinomas. BAG-1 expression was higher in low-grade carcinomas. In the carcinoma group there was a positive correlation (Pearson) between BCL-2 and cytoplasmic/nuclear BAG-1. In the hyperplasia group there was a negative correlation between BAX and BCL-2, and between AR and M30. We also detected a positive correlation between AR and nuclear/cytoplasmic BAG-1 and between nuclear and cytoplasmic BAG-1 in hyperplasias. BAG-1 showed the same specific basal cell localization as BCL-2 in hyperplastic and normal glands.

Conclusions

The BAG-1 protein showed a distinct distribution pattern in hyperplastic and neoplastic prostate. BAG-1 in association with BCL-2 inhibits apoptosis and may prolong the life of neoplastic cells and give them a chance to gain new oncogenic features in early carcinogenesis.